Preparation for magnesium ammonium phosphate cements

ABSTRACT

The invention relates to a preparation for a magnesium ammonium phosphate cement. There is provided a preparation comprising (a) a magnesium calcium phosphate of the formula Mg x Ca y (PO 4 ) 2 O z , wherein x+y≦4, x&gt;1, y&gt;0, z=x+y−3 and z≧0; (b) an ammonium salt; and (c) water; wherein the ammonium salt and the water can be present partially or completely as an aqueous solution of the ammonium salt.

The invention relates to a preparation for a magnesium ammoniumphosphate cement, a process for the production of such a cement, anduses of the so prepared cement.

The healing process of bone defects, the extent of which exceeds acritical size (critical size defects, CSD) requires application sitespecific the use of transplants or implants to prevent growing ofconnective tissue into the defect and to restore the lostbiofunctionality [1]. Regarding the growing-in behavior and diefunctional restoration the autologous transplantation of a body-own bonerepresents a “gold standard”; however, with large defects it has thedisadvantages of lacking availability and the risk of a second-lookoperation. Therefore, in recent years there were investigated syntheticbone replacement materials. In the clinical application these syntheticbone replacement materials have to fulfill different criteria. While inthe force-loaded area mainly mechanical properties are in the focus andhere primarily high-tensile metallic materials such as titanium,titanium alloys, stainless steels, and CoCr alloys are used importanceis attached to a connective tissue free growing in of the material, anda selective resorption and replacement by natural bone in the not oronly slightly force-loaded area. Artificial materials with clinicalapplication for such not functionally force-loaded defects are calciumphosphate ceramics [2, 3] and cements [4], respectively, bio-glasses [2,5], collagens [6, 7], or lyophilized bone implants. At the applicationsite the materials have to absorb mechanical load only partly and as themostly porous lead structure should support growing in of new bone.

A main clinical requirement to bone replacement materials is theirresorptivity in the physiologic environment regenerating native bonesubstance. Many of the mentioned materials cannot or only partiallyfulfill this requirement. For example, sintered ceramics of hydroxylapatite [8, 9, 10, 11], or cements of polymethyl methacrylate [12] donot show physiological degradability. Degradable materials with clinicalemployment are for example tricalcium phosphate ceramics [13] as powdersor granules which however, cannot take over a support function in thebone defect. Additionally, in situ formable and hardening mineralcements are known that on the one hand can set to hydroxyl apatite andthat only are resorbed over longer periods of time or compositions thatafter setting consist of calcium hydrogen phosphate-dihydrate (brushite)[14] and can be resorbed medium-term due to their comparatively highsolubility in a period of about 3 to 6 months [15, 16, 17]. Reservationsregarding a wide-ranging clinical application of such brushite cementsresult from the comparatively low mechanical strength as well as thestrongly acidic pH value of the materials during and after the settingprocess that can result in the release of acidic phosphate ions into thesurrounding tissue [18].

A further and new alternative represent magnesium ammonium phosphatecements which set within a short period of time (<5 to 10 min.) tomagnesium ammonium phosphate-hexahydrate ((NH₄)MgPO₄·6(H₂O), struvite).Struvite represents a biological calcification and is found, for exampleafter bacterial infection in nephroliths [19]. Cement formulationsforming struvite as setting product were repeatedly described inliterature [20, 21, 22, 23, 24] and showed very good mechanicalproperties with a compressive strength >50MPa and a setting time of 3 to10 min. Thereby, the setting reaction of the cements takes place in theneutral pH value range because both the powder components (MgHPO₄,Mg₃(PO₄)₂) and the liquid cement phase ((NH₄)₂HPO₄) are almost neutral.From the solubility product of struvite (LP=5.21×10⁻¹⁵ (pK(sp)=14.28) toLP=2.12×10⁻¹³ (pK(sp)=12.67) in the pH range of 7.01-9.62) [25] asubstantially better resorptivity in the region of the bone transplantcan be expected as for example from materials based on hydroxyl apatite(pK=59) or tricalcium phosphate (pK=29).

The studies about struvite cements known from the literature each usedmultiple-component powder mixtures of secondary (MgHPO₄) and tertiary(Mg₃(PO₄)₂) magnesium phosphates in association with calciumorthophosphates (α-TCP, β-TCP, HA) as fillers. For example, from DE 10032 220 A1 cement formulations with a Mg/P molar ratio of 0<Mg/P<0.50,and a Ca/P molar ratio of 0<Ca/P<1.50 are known.

Here, the use of multiple-component powder mixtures can result inproblems in view of the homogenous miscibility with different particlesizes or of separation processes in case of storage and transport of thematerials.

Object of the invention is to eliminate the disadvantages according tothe state of the art. In particular, a preparation for the production ofmagnesium ammonium phosphate cements should be provided that on the onehand have good mechanical properties, and high resorptivity, however onthe other hand use a one-component calcium and magnesium source so thata simplified preparation with a defined setting time is obtained.

This object is solved by the features of claims 1, 17, and 20. PracticalArrangements of the invention arise from the features of claims 2 to 16,18, 19, and 21 to 25.

In accordance to the invention there is provided a preparation for amagnesium ammonium phosphate cement comprising

(a) a magnesium calcium phosphate of the formulaMg_(x)Ca_(y)(PO₄)₂O_(z), wherein x+y≦4, x>1, y>0, z=x+y−3 and z≧0;(b) an ammonium salt; and(c) water;wherein the ammonium salt and the water may be present partially orcompletely as aqueous solution of the ammonium salt.

When x+y<3 then z is strictly 0. When x+y≧3 then z is in the range of 0to 1, wherein preferably z=0. In a particularly preferred embodimentx+y=3 and z=0.

The magnesium calcium phosphate has a Mg/P molar ratio in the range of0.5<Mg/P<2 and a Ca/P molar ratio in the range of 0<Ca/P<1.

Preferred is x>2. Further preferred are a magnesium calcium phosphatewith 2.0<x<2.75 or mixtures of magnesium calcium phosphates with2.0<x≦2.75.

The invention is based on the finding that a successive replacement ofmagnesium ions by calcium ions in the synthesis of compounds of the typeMg_(x)Ca_(y)(PO₄)₂O_(z) setting with aqueous ammonium phosphate solutionto struvite permits a defined adjustment of the setting time.

The hardened magnesium ammonium phosphate cements prepared by means ofthe preparation in accordance to the invention have a high strength, inparticular a compressive strength of more than 30 MPa after 24 h ofhardening at 37° C. For the production of the magnesium ammoniumphosphate cement the components of the preparation are mixed until ahomogenous mixture, the cement paste, is obtained. During the settingprocess the cement paste has a neutral or almost neutral pH value whatmakes physiological applications of the preparation easier. The hardenedmagnesium ammonium phosphate cement can be chemically resorbed in bodyelectrolyte what is attributable to the comparatively high solubility ofthe setting product struvite.

Preferably, the magnesium calcium phosphate is prepared from a mixtureconsisting of the compounds calcium hydrogen phosphate (CaHPO₄), calciumcarbonate (CaCO₃), magnesium hydrogen phosphate trihydrate(MgHPO₄·3H₂O), and magnesium hydroxide (Mg(OH)₂). Alternatively, othermagnesium or calcium compounds may be employed, for example CaO,Ca(OH)₂, CaHPO₄·2H₂O, Ca(NO₃)₂, MgO, MgCO₃, Mg(NO₃)₂, etc. For that,powdered compounds are mixed in a given stoichiometric ratio. Here, themixing ratio is selected such that the conditions for x and y and z inthe formula Mg_(x)Ca_(y)(PO₄)₂O_(z) are fulfilled. After homogenouslymixing the compounds the so obtained mixture is sintered to obtain theproduct with the formula Mg_(x)Ca_(y)(PO₄)₂O_(z). Preferably, sinteringis performed at temperatures of more than 800° C. and for a period oftime of 1-100 h. By means of sintering the magnesium calcium phosphateis obtained as a solid one-component compound. Here, the term“one-component” means a homogenous composition also in the microscopicscale, however in this case, several not distinctly identifiablecrystalline calcium and magnesium phosphate phases may be present in thesingle grains. Subsequently, the sinter cake is comminuted and thecomminuting product is grinded to a given initial particle size. Aftergrinding, the particle size should be 0.1 μm to ca. 100 μm, wherein itmight be of advantage to specifically combine fractions with differentparticle sizes. It is particularly preferred that the mean particle sizeof the powdery magnesium calcium phosphate is in the range of 0.5 to 10μm. By means of grinding, the magnesium calcium phosphate is obtained inthe form of a powder. Here, the grinding not only results in thecomminution of the magnesium calcium phosphate particles but also in apartial amorphization (mechanical activation) resulting in an increasedsolubility and reactivity of the magnesium calcium phosphate particleobtained by grinding.

Preferred magnesium calcium phosphates are e.g.,Mg_(2.25)Ca_(0.75)(PO₄)₂, Mg_(2.5)Ca_(0.5)(PO₄)₂, andMg_(2.75)Ca_(0.25)(PO₄)₂. Also mixtures of these compounds can beemployed. However, because the exemplarily given compositions are notdefined compounds in the sense of crystallography also deviatingcompositions of Mg, Ca, and (PO₄) can be chosen. Particularly preferredare compositions in accordance to the following formulaMg_(2.0-2.9)Ca_(0.1-1.0)(PO₄)₂.

Preferably, the preparation comprises the ammonium salt in the form ofan aqueous solution. For the production of the magnesium ammoniumphosphate cement the aqueous ammonium salt solution is then mixed withthe solid powdered magnesium calcium phosphate until a homogenousmixture is obtained. Hereinafter, the homogenous mixture is alsoreferred to as cement paste. The ratio of solid powdered magnesiumcalcium phosphate to the aqueous ammonium salt solution (powder/liquidratio) is preferably 1.0 to 5.0 g/ml, more preferred 2.5 to 5.0 g/ml,particularly preferred 2.5 to 3.5 g/ml.

Alternatively, the ammonium salt however may also be mixed with thepowdered magnesium calcium phosphate partially or completely as a solidpowdered ammonium salt. By doing so, a high powder/liquid ratio can beobtained in which case a solely solution of the ammonium salt due to itslimited solubility would not provide a sufficient concentration ofammonium ions for a complete setting. The thus obtained powdery solidmixture is then mixed with water to obtain the cement paste. The ratioof the solid powdery mixture of magnesium calcium phosphate and ammoniumsalt to water (powder/liquid ratio) is preferably 1.0 to 5.0 g/ml, morepreferred 2.5 to 5.0 g/ml, particularly preferred 2.5 to 3.5 g/ml.

Preferably, the ammonium salt is an ammonium phosphate, particularlypreferred a diammonium hydrogen phosphate. Preferably, the diammoniumhydrogen phosphate is present as a 3.5M aqueous solution. Alsoparticularly preferred are mixtures of diammonium hydrogen phosphate andammonium dihydrogen phosphate at comparable total concentration. Also,alternative ammonium salts can be used, for example in particular themonoammonium salts and/or the diammonium salts of citric acid, tartaricacid, sulfuric acid, and acetic acid, or their mixtures.

The production of the magnesium ammonium phosphate cement using thepreparation according to the invention preferably comprises thefollowing steps:

(a) mixing the magnesium calcium phosphate with the ammonium salt andthe water and/or with an aqueous solution of the ammonium salt until ahomogenous mixture (cement paste) is obtained;(b) application or introduction of the homogenous mixture to or in atarget object; and(c) causing the homogenous mixture to hard obtaining the settedmagnesium ammonium phosphate cement.

Preferably, in step (a) powdered magnesium calcium phosphate ishomogenously mixed with an aqueous solution of the ammonium salt.Preferably, the ammonium salt is diammonium hydrogen phosphate or amixture of diammonium hydrogen phosphate and ammonium dihydrogenphosphate, or ammonium dihydrogen phosphate.

The setting time of the cement paste can be adjusted by variousmechanisms. Reduction of the setting time is achieved either byextending the grinding period and/or by increasing the concentration ofthe ammonium salt in the preparation, for example by increasing itsconcentration in the aqueous solution. Alternatively, (in particularwhen the solubility limit is reached) a part (or all) of the ammoniumsalt can be incorporated into the powder component.

The viscosity of the cement paste may be decreased by reducing thepowder/liquid ratio so that the paste can also be injected through thincannulas whereby the mechanical properties are not deterioratedintensively as is known from calcium phosphate cements.

The preparation according to the invention is used for the production ofa magnesium ammonium phosphate cement. The magnesium ammonium phosphatecement can be employed for medical purposes, for example as bone cement,bone replacement, and/or as bone filler or bone adhesive. In addition,the magnesium ammonium phosphate cement can be used for the productionof preformed implants. Such implants may for example be prepared by 3Dpowder printing.

Basically, the combination of mineral bone cements with variousexcipients is known from the literature, in particular such excipientsthat can affect the injectivity, cohesion, paste consistency, porosity,resorptivity, adhesion to the bone, stability in storage, compatibilitywith active ingredients and their release in the desired manner. Allthese excipients can also be combined with the cement compositiondescribed herein.

The same applies for pharmacologic active ingredients. The magnesiumammonium phosphate cement according to the invention is particularlysuitable as supporting material for active ingredients since it iscomposed of largely pH neutral components and also the setting productreacts neutral. Particularly preferred is the combination of the cementwith active ingredients which promote the bone formation, suppressinflammatory reactions in the environment of the implanted material,suppress the bone resorption, and/or are suitable for the control ofmicrobial infections or contaminations.

The preparation according to the invention or the cement obtained bymeans of the preparation according to the invention can be combined withpharmaceutical active ingredients. Exemplary pharmaceutical activeingredients are antibiotics, bone growth factors, cytostatic agents, andanti-inflammatory agents, this list being not exhaustive.

When the pharmaceutical active ingredients are water-soluble they arepreferably added to the liquid phase of the preparation. Alternatively,the pharmaceutical active ingredients can be added to the obtainedcement. In this case, the pharmaceutical active ingredient may forexample be added to the powdery cement directly or encapsulated in adegradable polymer. By the encapsulation in a degradable polymer thereleasing kinetics of the pharmaceutical active ingredient can becontrolled advantageously.

Moreover, the preparation according to the invention or the cementobtained by means of the preparation according to the invention can becombined with excipients. Examples of excipients are viscosity affectingadditives for enhancing the injectivity as well as the cohesion of thecement paste, for example water-soluble polymers or multiple chargedanions for the electrostatic charging of the particles of the cement;particulate or fibrous ceramic or polymeric substances for thereinforcement of the cement matrix and for the formation of pores afterleaching, this list being not exhaustive.

The magnesium ammonium phosphate cement obtained from the preparationaccording to the invention has a high compressive strength and a goodresorptivity in the human or animal body.

The invention is explained in more detail below with reference toexamples.

EXAMPLES

The production of magnesium calcium phosphates according to theinvention was carried out by sintering powder mixtures with thestoichiometry given in table 1 at a temperature of 1,100° C. and asinter period of 5 h. Then, the sinter cake was comminuted manually to aparticle size<355 μm and grinded in a planetary ball mill for a periodof time of 10 min. to 24 h. The mean size of the obtained magnesiumcalcium phosphate particles is stated in table 2.

TABLE 1 Composition of the powder mixture for the production of thecompounds of the formula Mg_(x)Ca_(y)(PO₄)₂O_(z) (z = 0) CaHPO₄ CaCO₃MgHPO₄•3H₂O Mg(OH)₂ Mg_(x)Ca_(y)(PO₄)₂ [mol] [mol] [mol] [mol]Mg_(1.5)Ca_(1.5)(PO₄)₂ 1 0.5 1 0.5 Mg_(2.25)Ca_(0.75)(PO₄)₂ 0.5 0.25 1.50.75 Mg_(2.5)Ca_(0.5)(PO₄)₂ 0.33 0.17 1.67 0.83 Mg_(2.75)Ca_(0.25)(PO₄)₂0.167 0.083 1.83 0.92 *Mg₃(PO₄)₂ — — 2 1 *Comparative example

TABLE 2 Mean Particle Size in μm of Mg_(x)Ca_(y)(PO₄)₂O_(z) (z = 0)Grinding period [h] Mg_(1.5)Ca_(1.5)(PO₄)₂ Mg_(2.25)Ca_(0.75)(PO₄)₂*Mg₃(PO₄)₂ not grinded 41.1 ± 14.2 23.8 47.8 ± 1.3 1 h 16.2 ± 1.6  7.7 ±0.2 10.5 ± 2.6 4 h 7.3 ± 3.0 6.09 ± 0.1   7.5 ± 0.4 24 h  5.1 ± 1.1 0.6± 0.1  2.7 ± 1.7 *Comparative example

The thus obtained powders were mixed with a 3.5M aqueous (NH₄)₂HPO₄solution as the liquid phase into a cement paste. Here, thepowder/liquid ratio (P/L) was varied in the range of 1.0 to 3.5 g/ml.The setting times of the cement paste were determined by the Gilmoreneedle test at 37° C. and >90% relative humidity (tables 3 and 4).

TABLE 3 Setting times of a cement paste of Mg_(x)Ca_(y)(PO₄)₂O_(z) (z =0) and a 3.5M (NH₄)₂HPO₄ solution as the liquid phase (P/L = 3.0 g/ml),measured by the Gilmore needle test Grinding period [h]Mg_(1.5)Ca_(1.5)(PO₄)₂ Mg_(2.25)Ca_(0.75)(PO₄)₂ *Mg₃(PO₄)₂ 1 h 32 min.14 min. 4 min. *Comparative example

TABLE 4 Setting times of a cement composition of Mg_(x)Ca_(y)(PO₄)₂O_(z)(z = 0) with a 3.5M (NH₄)₂HPO₄ solution as the liquid phase independence on the powder/liquid ratio (P/L), measured by the Gilmoreneedle test Mg_(2.5)Ca_(0.5)(PO₄)₂ Mg_(2.75)Ca_(0.25)(PO₄)₂ 1 h 4 h 1 h4 h P/L Grinding Grinding Grinding Grinding [g/ml] period period periodperiod 3.0  8 min.  4 min.  8 min. 3 min. 30 sec. 2.5 13 min.  8 min. 12min. 6 min. 30 sec. 2.0 18 min. 13 min. 19 min. 14 min. 1.5 22 min. 19min. 23 min. 18 min.

For the determination of the compressive strength of the magnesiumammonium phosphate cements prepared by means of the preparationaccording to the invention the cement paste was filled into siliconemoulds and hardened for 24 h at 37° C. Cartesian specimens of thedimension of 12×6×6 mm resulted which were loaded with an universal testmachine along the longitudinal axis until breaking. The compressivestrength was calculated from the breaking strength and thecross-sectional area (tables 5 and 6).

TABLE 5 Compressive strength of magnesium ammonium phosphate cementsprepared from Mg_(x)Ca_(y)(PO₄)₂O_(z) (z = 0) and a 3.5M (NH₄)₂HPO₄solution as the liquid phase (P/L = 3.0 g/ml) after 24 h of hardening at37° C. and 100% relative humidity Grinding period¹ [h]Mg_(1.5)Ca_(1.5)(PO₄)₂ Mg_(2.25)Ca_(0.75)(PO₄)₂ Mg_(2.5)Ca_(0.5)(PO₄)₂Mg_(2.75)Ca_(0.25)(PO₄)₂ *Mg₃(PO₄)₂ 1 h 16.0 ± 2.8 42.3 ± 9.6 21.8 ± 4.025.7 ± 4.3 61.2 ± 6.0 4 h 21.2 ± 3.5 72.7 ± 8.8 77.1 ± 6.4 53.8 ± 6.358.6 ± 9.5 24 h  — — — — 42.3 ± 9.6 ¹grinding period of the statedsintered magnesium calcium phosphate *Comparative example — notdetermined

TABLE 6 Compressive strength of magnesium ammonium phosphate cementsprepared from Mg_(x)Ca_(y)(PO₄)₂O_(z) (z = 0) powdered by use ofdifferent grinding periods and a 3.5M (NH₄)₂HPO₄ solution as the liquidphase with different powder/liquid ratios (P/L) after 24 h of hardeningat 37° C. Mg_(2.5)Ca_(0.5)(PO₄)₂ Mg_(2.75)Ca_(0.25)(PO₄)₂ 1 h 4 h 1 h 4h P/L Grinding Grinding Grinding Grinding [g/ml] period period periodperiod 3.0  21.8 ± 4.01 77.1 ± 6.4 25.7 ± 4.3 53.8 ± 6.3 2.5 17.4 ± 4.155.6 ± 7.4 20.3 ± 4.3 52.7 ± 6.6 2.0 16.7 ± 6.8 15.2 ± 4.9 15.3 ± 4.912.2 ± 5.4 1.5 12.4 ± 4.3 15.0 ± 4.5 13.7 ± 4.5 15.0 ± 4.7

LITERATURE

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1. A preparation for a magnesium ammonium phosphate cement comprising:(a) a magnesium calcium phosphate of the formulaMg_(x)Ca_(y)(PO₄)₂O_(z), wherein x+y≦4, x>1, y>0, z=x+y−3 and z≧0; (b)an ammonium salt; and (c) water; wherein the ammonium salt and the watercan be present partially or completely as an aqueous solution of theammonium salt.
 2. The preparation according to claim 1 wherein themagnesium calcium phosphate has a Mg/P molar ratio in the range of0.5<Mg/P<2.0 and a Ca/P molar ratio in the range of 0<Ca/P<1.
 3. Thepreparation according to claim 1 wherein x≧2.
 4. The preparationaccording to claim 1 wherein the magnesium calcium phosphate is amagnesium calcium phosphate of the formulaMg_(2.0-2.9)Ca_(0.1-1.0)(PO₄)₂ or a mixture of magnesium calciumphosphates of this formula.
 5. The preparation according to claim 3wherein the magnesium calcium phosphate is a magnesium calcium phosphatewith 2.0<x≦2.75 or a mixture of magnesium calcium phosphates with2.0<x≦2.75.
 6. The preparation according to claim 5 wherein themagnesium calcium phosphate is selected from the group comprisingMg_(2.25)Ca_(0.75)(PO₄)₂, Mg_(2.5)Ca_(0.5)(PO₄)₂,Mg_(2.75)Ca_(0.25)(PO₄)₂, and mixtures thereof.
 7. The preparationaccording to claim 1 wherein the magnesium calcium phosphate is asintered magnesium calcium phosphate.
 8. The preparation according toclaim 1 wherein the magnesium calcium phosphate is powdery and has amean particle size in the range of 0.5 to 10 μm.
 9. The preparationaccording to claim 1 wherein the ammonium salt is selected from thegroup comprising monoammonium salts of phosphoric acid, monoammoniumsalts of citric acid, monoammonium salts of tartaric acid, monoammoniumsalts of sulfuric acid, monoammonium salts of acetic acid, diammoniumsalts of phosphoric acid, diammonium salts of citric acid, diammoniumsalts of tartaric acid, diammonium salts of sulfuric acid, anddiammonium salts of acetic acid, and mixtures thereof.
 10. Thepreparation according to claim 1 wherein the ammonium salt is chosenfrom the group comprising diammonium hydrogen phosphate, ammoniumdihydrogen phosphate, and a mixture of this two salts diammoniumhydrogen phosphate and ammonium dihydrogen phosphate.
 11. Thepreparation according to claim 10 wherein the ammonium salt is presentas a 3.5M aqueous solution.
 12. The preparation according to claim 5wherein the ammonium salt is admixed to the magnesium calcium phosphatepartially or completely in solid form as a powder.
 13. The preparationaccording to claim 1 wherein the ratio of magnesium calcium phosphate towater or to the aqueous solution is 1.0 to 5.0 g/ml.
 14. The preparationaccording to claim 1 wherein the preparation further comprisespharmaceutically active ingredients.
 15. The preparation according toclaim 1 wherein the preparation further comprises viscosity affectingexcipients.
 16. The preparation according to claim 1 wherein thepreparation further comprises pore forming excipients.
 17. A process forthe production of a magnesium ammonium phosphate cement using apreparation comprising: (a) mixing magnesium calcium phosphate withammonium salt and the water or with an aqueous solution of the ammoniumsalt until a homogenous mixture is obtained; (b) applying of thehomogenous mixture to a target object; and (c) causing the homogenousmixture to harden, thereby obtaining set magnesium ammonium phosphatecement.
 18. The process according to claim 17 wherein step (a) comprisesmixing of the magnesium calcium phosphate with the aqueous solution ofthe ammonium salt.
 19. The process according to claim 17 wherein theammonium salt in step (a) is present partially or completely as powder.20. (canceled)
 21. The process according to claim 17, wherein themagnesium ammonium phosphate cement is used for medical purposes. 22.The process according to claim 21, wherein the magnesium ammoniumphosphate cement is used for at least one of the group comprising bonereplacement, bone filler, and bone adhesive.
 23. The process accordingto claim 21 wherein the magnesium ammonium phosphate cement is used fora preformed implant.
 24. The process according to claim 17 wherein thepreparation or the magnesium ammonium phosphate cement acts as a supportfor pharmaceutically active ingredients.
 25. The preparation useaccording to any one claim 1 wherein the preparation or the magnesiumammonium phosphate cement further comprises at least one chosen from thegroup comprising viscosity affecting and pore forming excipients.
 26. Apreparation for a magnesium ammonium phosphate cement comprising: (a) amagnesium calcium phosphate of the formula Mg_(x)Ca_(y)(PO₄)₂O_(z),wherein x+y≦4, x>1, y>0, z=x+y−3 and z>0, wherein the magnesium calciumphosphate is chosen from the group comprising sintered magnesium calciumphosphate, powdery magnesium calcium phosphate having a mean particlesize in the range of 0.5 to 10 μm, Mg_(2.25)Ca_(0.75)(PO₄)₂,Mg_(2.5)Ca_(0.5)(PO₄)₂, and Mg_(2.75)Ca_(0.25)(PO₄)₂; (b) an ammoniumsalt, wherein the ammonium salt is selected from the group comprisingmonoammonium salts of phosphoric acid, monoammonium salts of citricacid, monoammonium salts of tartaric acid, monoammonium salts ofsulfuric acid, monoammonium salts of acetic acid, diammonium salts ofphosphoric acid, diammonium salts of citric acid, diammonium salts oftartaric acid, diammonium salts of sulfuric acid, diammonium salts ofacetic acid, and mixtures thereof, diammonium hydrogen phosphate,ammonium dihydrogen phosphate, and a mixture of diammonium hydrogenphosphate and ammonium dihydrogen phosphate; (c) water, wherein theammonium salt and the water can be present partially or completely as anaqueous solution of the ammonium salt; and, (d) at least one of thegroup comprising pharmaceutically active ingredients, viscosityaffecting excipients, pore forming excipients, injectivity affectingexcipients, cohesion affecting excipients, paste consistency affectingexcipients, porosity affecting excipients, resorptivity affectingexcipients, adhesion to the bone affecting excipients, stability instorage affecting excipients, compatibility with active ingredientsaffecting excipients, and release affecting excipients.